For the proposed Pharmacokinetic Center, it is our intent as part of the North American Brain Tumor Consortium (NABTC, Central Operations Office) to derive pharmacological information on selected anticancer agents in phase I/II clinical trials for the treatment of CNS malignancies. The drugs to be studied and the extent of each study will be determined by the Group Leader (Michael Prados, M.D., UCSF). For the pharmacokinetic studies, the work will consist of four phases: (a) Design of an appropriate pharmacokinetic sampling procedure for inclusion in the NABTC protocol. (b) Develop or implement a suitable analytical method for the measurement of likely tissue and biological fluids. Specifically, HPLC or LC/MS validated methodologies will be established for real time quantitation of the compound (such as CCI-779 & ZD1839) being studied. (c) Provision of the pharmacokinetic parameters including maximum plasma or tissue concentration; plasma or clearance; apparent volume of distribution at steady state; area under the plasma time curve; tissue distribution and harmonic mean plasma half-lives. Attempts will be made to correlate these pharmacokinetic parameters with the observed biological effects such as toxicity, response or biological surrogate marker data. Generally these studies will be confined to the parent drug. However, in instances where extensive metabolism occurs, the development of analytical methodology for measurement of the metabolites will be pursued so that parallel pharmacokinetic/pharmacodynamic determinations of these compounds can be conducted along with the apparent compound. [unreadable] [unreadable] [unreadable]